Detecting and treating disordered breathing

ABSTRACT

A system for treating disordered breathing of a human being includes an implantable transvenous stimulation lead having at least one stimulation electrode and a sensor configured to detect activity level of the human being. The system includes an energy source, a pulse generator and circuitry, the circuitry operative to receive a signal indicative of the activity level of the human being from the sensor, wherein the circuitry is configured to cause the energy source and the pulse generator to deliver spaced apart stimulation signals to the at least one stimulation electrode while the activity level of the human being is sufficiently low to be indicative of sleep. Spaced apart stimulation pulses from the electrode are configured to extend a duration of a time of at least one breath being defined as the time from an onset of inhalation to the onset of inhalation of a successive breath.

CROSS REFERENCE TO RELATED CASES

The present application is a continuation of U.S. application Ser. No.12/163,500, entitled DETECTING AND TREATING DISORDERED BREATHIN that wasfiled on Jun. 27, 2008, now issued as U.S. Pat. No. 9,987,488, whichclaims the benefit of U.S. Provisional Application entitled “ALGORITHMSFOR PHRENIC NERVE STIMULATION” file Jun. 27, 2007, Ser. No. 60/937,426,the contents of both applications being incorporated by reference intheir entireties.

FIELD OF THE INVENTION

The present invention relates to detecting and treating defects in humanrespiration, particularly the types of disordered breathing that mayaccompany heart disease.

BACKGROUND

Human respiration is an extraordinarily complicated process. Althoughrhythmic breathing, inhalation and exhalation, is familiar to all of us,the underlying processes that give rise to the observed respirationcycle are complex. In general respiration permits gas exchange betweengases in the blood and gases in the environment. In a healthyindividual, oxygen is provided to the blood and carbon dioxide, which isa product of metabolic processes in the body, is driven off into theatmosphere. Respiration is subject to both voluntary and involuntarycontrol and several disease processes can have a profound impact onrespiration.

A person's respiration is controlled by the autonomic nervous systemthat integrates inputs from many physiologic sensors such asmechanoreceptors and chemoreceptors. The central nervous system commandsthe diaphragm and other muscles in the chest as well as in the neck tophasically contract and relax thus producing a breath of certain shapeand tidal volume. It also acts as a respiratory pacemaker by setting thebreathing rate. In a normal sleeping person the next breath is typicallyinitiated substantially immediately after the previous breath iscompletely exhaled. The term tidal volume refers to the volume of airinspired or expired during a respiratory cycle. Together tidal volumeand breathing rate determine minute volume of ventilation thatdetermines the rate at which oxygen is delivered and CO₂ is removed fromthe respiratory system.

The term disordered breathing is used herein to describe a variety ofobservable respiration patterns that deviate from normal respiration.For example, Cheyne-Stokes respiration (“CSR”) is clinically observedand declared when a patient has bouts of “rapid” and/or “deep” breathingfollowed by reductions in breathing or apnea-hypopnea. This abnormalpattern of breathing can be seen in patients with strokes, traumaticbrain injuries, brain tumors, and congestive heart failure and isusually a result of poor control of blood gas chemistry by the centralnervous system.

“Pure” Cheyne-Stokes respiration is also called central sleep apnea bythe medical community and is sometimes present with congestive heartfailure. However, CSR breathing may be mixed with other respirationdisorders that may or may not be related to congestive heart failure orother cardiac disorders.

SUMMARY

Embodiments in accordance with the present invention are directed todetecting and treating disordered breathing. In some embodiments, adevice may operate by sensing natural respiration and phasicallysynchronizing the delivery of a stimulus with the breath afterinspiration. The stimulation of these embodiments is provided to atleast one half of a patient's phrenic nerves which innervate one side ofthe diaphragm associated with one lung. The stimulus is of a sufficientcharacter to cause that lung to “be still,” with some amount of airretained in the lung, and lung volume generally will not change duringthe stimulation, within some broadly defined limits. It is the belief ofthe inventors that it may be sufficient to stimulate and still only onelung under the theory that compensatory physiologic feedback mechanismspreserved on the unstimulated lung of the central and autonomic nervoussystem will interact in a virtuous and favorable way with thestimulation regime to provide the therapy.

It is believed that arresting at least one lung will prolong breaths andthus temporarily slow respiration and modify or modulate the tidalvolume of breathing. This reduction of tidal volume may prevent bloodcarbon dioxide from being driven to low levels associated with apnea.

In other embodiments in accordance with the present invention, thestimulus is applied to still at least one lung upon detection of anapnea-hypopnea of some length or upon the detection of hyperpnea. Inthese embodiments, the stimulation may be initiated during theapnea-hypopnea period or upon detection of a breath of a predeterminedintensity near the end of apnea-hypopnea. The stimulation may beinitiated in phase with respiration or irrespective of the phase ofrespiration. If initiated irrespective of the phase of respiration, thestimulation may be gradually increased in intensity so as to expand andstill at least one lung slowly so as not to disturb or arouse a sleepingpatient. For purposes of this discussion, hyperpnea is defined asabnormally rapid or deep breathing. In some but not all cases, hyperpneamay involve rapid breathing that is compensating for the reducedrespiratory effectiveness of a previous period of apnea-hypopnea orreduced breathing.

Embodiments in accordance with the present invention may cooperate withnaturally occurring physiologic feedback mechanisms to provide a therapyfor disordered breathing. In one embodiment, a fully implanted devicecoupled to a transvenous lead system may be provided to monitorbreathing and extract inspiration points, expiration points and otherdata associated with a physiologic breathing pattern. A programmablecomputer may be provided with control software for managing both therespiration measuring system as well as extracting useful dataconcerning breathing. The programmable computer may be described as acombination of circuitry and software, circuitry and firmware, or acomputer with software or firmware, and all of these descriptionscontemplate the same essential elements. The control software within thedevice may select the timing for the delivery of hemi diaphragmaticstimulation and accept input information from a variety of sources thatcan be used in nested control loops to tailor the therapy to aparticular patient and to provide a different therapy as the patient'sneeds change.

In one embodiment in accordance with the invention, a system fortreating disordered breathing includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. In this embodiment, the circuitry is operativeto monitor signals from the respiration sensor and detectapnea-hypopnea. The circuitry will deliver a stimulation signal to thestimulation electrode after the detection of apnea-hypopnea. In thisembodiment, the stimulation signal has a duration of at least tenseconds.

In another embodiment in accordance with the invention, a system fortreating disordered breathing includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. In this embodiment, the circuitry is operativeto monitor signals from the respiration sensor and detectapnea-hypopnea. The circuitry will deliver a stimulation pulse to thestimulation electrode after the detection of a hyperpnea followingapnea-hypopnea. In this embodiment, the stimulation signal has aduration of at least ten seconds.

In yet another embodiment in accordance with the invention, a system fortreating disordered breathing includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. In this embodiment, the circuitry is operativeto monitor signals from the respiration sensor and detect apnea-hypopneaby accumulating data from the respiration sensor to determine a valuerepresentative of average tidal volume and then detecting hyperpneawhen, for example, the measured value is below 30% of the average valuefor ten seconds. The circuitry will deliver a stimulation pulse to thestimulation electrode after the detection of apnea-hypopnea. In thisembodiment, the stimulation signal has a duration of at least tenseconds.

In yet another embodiment in accordance with the invention, a system fortreating disordered breathing includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. In this embodiment, the circuitry is operativeto monitor signals from the respiration sensor and detect apnea-hypopneaby accumulating data from the respiration sensor to determine a valuerepresentative of average tidal volume and then detecting hyperpnea whenthe measured value is below 30% of the average value for ten seconds.The circuitry will then detect hyperpnea when the value representativeof tidal volume exceeds 30% of the average value after the detection ofapnea-hypopnea. The circuitry will deliver a stimulation pulse to thestimulation electrode after the detection of hyperpnea followingapnea-hypopnea. In this embodiment, the stimulation signal has aduration of at least ten seconds.

In another embodiment in accordance with the invention, a system fortreating disordered breathing includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. In this embodiment the stimulation lead isconfigured to be implanted in a blood vessel proximate a phrenic nervein a patient. In this embodiment, the circuitry is operative to monitorsignals from the respiration sensor and detect apnea-hypopnea. Thecircuitry will deliver a stimulation pulse to the stimulation electrodeafter the detection of apnea-hypopnea. In this embodiment, thestimulation signal has a duration of at least ten seconds.

A system for treating disordered breathing in accordance withembodiments of the invention includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. The circuitry of this embodiment is operativeto determine the onset of a hyperpnea based on the respiration sensorsignals and deliver a stimulation signal to the stimulation electrodeduring hyperpnea, the signal having a duration of at least one second toextend the duration of the breath.

Another system for treating disordered breathing in accordance withembodiments of the invention includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. The system receives signals from therespiration sensor and calculates a baseline breath duration. Thecircuitry of this embodiment is operative to determine the onset of ahyperpnea based on the respiration sensor signals and deliver astimulation signal to the stimulation electrode during hyperpnea, thesignal having a duration of at least 25% of the baseline breathduration.

Another system for treating disordered breathing in accordance withembodiments of the invention includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. The circuitry of this embodiment is operativeto determine the onset of a hyperpnea and the peak of inspiration basedon the respiration sensor signals and deliver a stimulation signal tothe stimulation electrode during hyperpnea proximate the peak ofinspiration, the signal having a duration of at least one second toextend the duration of the breath.

A system for treating disordered breathing in accordance withembodiments of the invention includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. The circuitry of this embodiment is operativeto determine the onset of a hyperpnea based on the respiration sensorsignals and to determine the duration of a hyperpnea cycle and deliver astimulation signal to the stimulation electrode during hyperpnea, thesignal having a duration greater than 25% of the duration of thehyperpnea cycle.

Another system for treating disordered breathing in accordance withembodiments of the invention includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. The circuitry of this embodiment is operativeto determine the onset of a hyperpnea based on the respiration sensorsignals and to determine the duration of a hyperpnea cycle. Thecircuitry is also operative to deliver a stimulation signal to thestimulation electrode during hyperpnea, the signal being initiated afterthe midpoint of the hyperpnea cycle and having a duration of at leastone second to extend the duration of the breath. In some variations ofthis embodiment the signal is initiated proximate the peak ofinspiration of a breath that occurs after the midpoint of hyperpnea.

Another system for treating disordered breathing in accordance withembodiments of the invention includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. The circuitry of this embodiment is operativeto determine the onset of a hyperpnea based on the respiration sensorsignals and to determine the duration of a hyperpnea cycle. Thecircuitry is also operative to deliver a stimulation signal to thestimulation electrode during hyperpnea, the signal being initiated afterthe midpoint of the hyperpnea cycle and having a duration of at leastone second to extend the duration of the breath. The circuitry of thisembodiment is also operative to deliver a stimulation signal at the peakof inspiration for several breaths beginning after the midpoint ofhyperpnea.

Another system for treating disordered breathing in accordance withembodiments of the invention includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. The circuitry of this embodiment is operativeto determine the onset of a hyperpnea based on the respiration sensorsignals. The circuitry is also operative to deliver at least threesegmented stimulation signals to the stimulation electrode during thehyperpnea.

Another system for treating disordered breathing in accordance withembodiments of the invention includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. The circuitry of this embodiment is operativeto determine the onset of a hyperpnea based on the respiration sensorsignals and to determine the average duration of a hyperpnea cycle andthe average duration of an apnea-hypopnea cycle. The circuitry is alsooperative to deliver a stimulation signal to the stimulation electrodeduring hyperpnea based on the average duration of a hyperpnea cycle andestablish a blanking period based on the average duration of anapnea-hypopnea cycle.

A system for treating disordered breathing in accordance withembodiments of the invention includes a stimulation lead having astimulation electrode, a respiration sensor, an energy source, a pulsegenerator, and circuitry. The circuitry of this embodiment is operativeto determine the onset of a hyperpnea based on the respiration sensorsignals and deliver a stimulation signal to the stimulation electrodeduring hyperpnea, where the signal has a duration of at least one secondand is in the form of a gradually rising and descending pulse trainenvelope.

In another embodiment in accordance with the invention, a method ofmonitoring or treating disordered breathing includes calculating anaverage duration of a patient's hyperpnea over some period of time andstimulating a diaphragm of the patient upon detection of hyperpnea. Inthis embodiment the stimulation lasts at least 30% as long as thecalculated average duration of hyperpnea.

Another embodiment in accordance with the invention involves a method ofmonitoring or treating disordered breathing. The method includesgathering data related to a patient's breathing and generating a valuerepresentative of the tidal volume of the breaths of the patient. Thetidal volumes of sequential breaths are compared and hyperpnea isdetected when there are three sequential breaths where the tidal volumeof each breath is at least 20% greater than the tidal volume of theprevious breath. The method of this embodiment includes calculating anaverage duration of a patient's hyperpnea over some period of time andstimulating a diaphragm of the patient upon detection of hyperpnea. Inthis embodiment the stimulation lasts at least 30% as long as thecalculated average duration of hyperpnea.

In another embodiment in accordance with the invention, a method ofmonitoring or treating disordered breathing includes calculating anaverage duration of a patient's hyperpnea over some period of time andstimulating a diaphragm of the patient upon detection of hyperpnea. Inthis embodiment the stimulation lasts at least 30% as long as thecalculated average duration of hyperpnea. The stimulation signal of thisembodiment is in the form of a gradually rising and descending pulsetrain envelope. Some examples of possible pulse train shapes includelinear, parabolic, and elliptical.

In yet another embodiment in accordance with the invention, a method ofmonitoring or treating disordered includes calculating an averageduration of a patient's episodes of hyperpnea over some period of timeand an average midpoint of the hyperpnea episode and stimulating adiaphragm of the patient during hyperpnea after the midpoint of thehyperpnea.

In yet another embodiment in accordance with the invention, a method ofmonitoring or treating disordered includes calculating an averageduration of a patient's episodes of hyperpnea over some period of timeand an average midpoint of the hyperpnea episode and stimulating adiaphragm of the patient during hyperpnea after the midpoint of thehyperpnea. This embodiment includes determining the peak of inspirationand stimulating proximate the peak of inspiration.

In yet another embodiment in accordance with the invention, a method ofmonitoring or treating disordered includes calculating an averageduration of a patient's episodes of hyperpnea over some period of timeand an average midpoint of the hyperpnea episode and stimulating adiaphragm of the patient during hyperpnea after the midpoint of thehyperpnea. In this embodiment additional future breaths extending beyondthe normal duration of hyperpnea are stimulated.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a stylized representation of tidal volume and chest motionover time of a patient.

FIG. 2 is a representation of a system as it interacts with a patient'srespiratory system.

FIG. 3 is a stylized representation of tidal volume, airflow, and anillustrative stimulation therapy.

FIG. 4 is a stylized representation of a stimulation protocol.

FIG. 5 is a stylized representation of tidal volume during a CSR cyclewith mixed apnea and several treatment protocols.

FIG. 6 is a stylized representation of tidal volume during a CSR cyclewith mixed apnea and several treatment protocols.

FIG. 7 is a flowchart of a detection and treatment protocol.

FIG. 8 is a flowchart of a detection and treatment protocol.

FIG. 9 is a flowchart of a stimulation adjustment protocol.

FIG. 10 is a flowchart of a stimulation adjustment protocol.

FIG. 11 is a flowchart of a breath detection protocol.

FIG. 12 is a flowchart of a breath detection protocol.

FIG. 13 is a flowchart of an apnea-hypopnea detection protocol.

FIG. 14 is a flowchart of a hyperpnea detection protocol.

FIG. 15 is a flowchart of a hyperpnea detection protocol.

FIG. 16 is a representation of a stimulation signal.

FIG. 17 shows experimental results of treatment of disordered breathing.

FIG. 18 shows experimental results of treatment of disordered breathing.

DETAILED DESCRIPTION

Turning now to the Figures, FIG. 1 is a stylized representation of tidalvolume and chest motion over time of a patient suffering from mixedapnea within Cheyne-Stokes Respiration. The CSR cycle 101 consists of anapnea-hypopnea period 102 and a hyperpnea period 103. Duringapnea-hypopnea 102 there is substantially no airflow 104 inspired orexpired. During hyperpnea 103 airflow gradually increases, crests andthen decreases from breath to breath. This pattern is often described asa crescendo-decrescendo pattern. In the beginning of apnea-hypopnea 106there is no respiratory drive from the autonomic nervous system of thepatient and consequently no substantial diaphragm or chest motion. Thisis an example of true or pure central sleep apnea. It may be caused bythe suppression of drive to breathe caused by the concentration of CO₂in the blood (“PaCO₂”) crossing below an apnic threshold. Thisabnormally low PaCO₂ is likely a result of the preceding hyperpnea 108that is in turn a manifestation of a ventilatory overshoot.

Respiratory or ventilatory overshoot describes an excessive response ofthe physiologic respiratory control system to a sensed change of bloodgas composition. In some disordered breathing patients, poor blood flowto the brain causes the central nervous system to perceive CO₂ levels inthe blood that are no longer representative of the overall blood CO₂level. In the case of high sensed CO₂ levels, the central nervous systemtriggers an increase in respiration in response to the high sensed CO₂levels, but by the time the chemoreceptors sense the reduced CO₂ leveland begin slowing respiration, the CO₂ levels have already become toolow. The CO₂ levels may drop below an apnic threshold and as a resultrespiration may stop or become reduced for a time. CO₂ levels increaseduring this period of reduced respiration and the cycle ofovercorrection of blood gas composition continues or becomes worse.Respiratory overshoot is manifested as excessive minute ventilation orhyperpnea that leads to apnea-hypopnea within the CSR cycle.

Later in the cycle, the patient's respiratory drive is restored 109 bythe increasing blood PaCO₂. Chest motion 109 indicates the presence ofrespiratory drive, but the patient is breathing against the closedairway. No airflow is present. This is obstructive apnea within the sameCSR cycle. Later in the cycle the patient's airway opens 110 and chestmotion is accompanied by airflow. The natural control system of therespiration in the patient overreacts to the prolonged apnea-hypopnea.Breathing gradually becomes deeper. This is a new cycle of hyperpnea.Excessive escalation of breathing control is the manifestation ofanother respiratory overshoot.

FIG. 2 is a representation of a system in accordance with embodiments ofthe invention as it interacts with a patient's respiratory system. Apatient's respiration is monitored 203 by a respiratory sensor that canbe, for example, an impedance sensor, a pressure sensor or anaccelerometer. A respiratory waveform can be acquired and stored in thesystem memory. Embedded software analyzes the waveform 204 and detectsparameters of a breath such as the breath phase (inspiration orexpiration) and tidal volume. At the appropriate time in the breathcycle, such as for example the end of inspiration, a pulse train orsignal of stimulation is applied by the stimulation generator 205 to aphrenic nerve. In this embodiment, the pulse train is of sufficientenergy to keep one hemidiaphragm muscle contracted (somewhat flattened)thus trapping some amount of air in at least one lung of the patient'srespiratory system 202. This pattern of stimulation results in theinhibition of respiration 206 that may temporarily prevent the naturalrespiratory pacemaker 201 of the patient from initiating a new breath.It is believed that this may be at least partially accomplished via avagal feedback into the autonomic control 201 system of the patient fromthe stretch receptors (mechanoreceptors) of the lung. As a result, thebreathing rate of the patient is momentarily reduced. This reductionresults in the suppression of respiratory overshoot that would otherwisebe caused by the unstable autonomic control. Prevention or reduction ofthe overshoot may prevent PaCO₂ from dropping below the apnic threshold.This may prevent the cessation or clinically undesirable reduction ofbreathing during the apnea-hypopnea phase of the CSR cycle.

The described basic operation of the detection and therapy deliveryprocesses of this embodiment can be supplemented by additional controlloops to make any stimulation device or other therapy delivery devicemore practical. For example, software can analyze 207 the respiratorywaveform acquired and stored in the device memory for breathingparameters such as respiratory rate, tidal volume, cyclic changes oftidal volume (crescendo-decrescendo), and periodicity of respiration.Based on these parameters the software can determine the settings forthe stimulation generator 205. For example, the duration of thestimulation train 208 can be determined based on the respiratory rate oron the success of the previous cycles of therapy. The stimulationduration can be automatically set to some number between, for example,0.5 and 60 seconds, thus determining how long the respiratory drive willbe suppressed. Based on the available data from the analysis of storedwaveforms, the software can also turn therapy on and off 209 or decideto extend one breath or a number of breaths. In one illustrativeembodiment stimulation is applied for the duration of a hyperpnea cycle.

In a further embodiment the software can calculate the respiratoryeffort breath-to-breath 210 based, for example, on the detected chestmotion 203. Software can adjust stimulation energy 211 by changing, forexample, settings for pulse current, signal duration or pulse frequencydepending of the detected breath pattern. As used herein, the terms“stimulation signal,” “stimulation,” “stimulation pulse train,” andequivalents refer to a single pulse or a train of pulses thatoperatively act as a single stimulation event.

In one embodiment in accordance with the invention, one hemidiaphragm ofthe patient is stimulated and remains in a relatively contracted statewhile the other can be naturally relaxed. This results in the trappingof a certain amount of air in the stimulated lung, which may even remainsubstantially inflated during stimulation. The level of stimulation maybe chosen to keep the lung sufficiently inflated so that the stretchreceptors in the lung act to activate the afferent vagal feedback to thepatient's natural respiration control center in the autonomic nervoussystem. This feedback may suppress the patient's natural drive tobreathe during the stimulation, and for a short time after thestimulation is ended, until both lungs are fully deflated. When the term“stimulated lung” is mentioned, it refers to the lung associated with astimulated hemidiaphragm or the lung associated with a stimulatedphrenic nerve. The term “stimulated lung” is used to simplify thedescription, and the stimulation of the corresponding hemidiaphragm orphrenic nerve is implied. “Unstimulated lung” can refer to an instancewhere no stimulation is applied or to a lung that is contralateral to astimulated lung. It is understood that unless otherwise specified, boththe right and left hemidiaphragms and/or phrenic nerves may bestimulated separately and independently, in combination, or inalternating patterns.

Whether or not the stimulation energy is sufficient to activate thisvagal afferent feedback, the stimulated breath is extended. Thebreathing rate and minute ventilation are momentarily reduced. Thisresults in the reduction of respiratory overshoot and consequentiallymay prevent blood PaCO₂ (Arterial blood carbon dioxide concentration)from dropping below an apnic threshold. As a result, the apnic phase ofthe CSR cycle may be prevented or substantially reduced in durationand/or severity.

Software can identify the cyclic breathing or CSR that is a periodicalternation of apnea-hypopnea and hyperpnea phases that together form aCSR cycle. Within the cycle software can identify apnea-hypopnea that isa cessation of breathing for several breaths or several sequentialbreaths of very week breathing. Software can identify the onset ofhyperpnea that is a sequence of breaths with sequentially increasingtidal volume following apnea-hypopnea. Software can extend one orseveral breaths in the beginning or middle of hyperpnea phase of thecycle.

Software can analyze the stimulated breaths for the effects ofstimulation. These effects can include the additional inhaled volume,duration and presence of a plateau and the increased stimulated breathduration. Software can compare the results of stimulation to the desiredsettings, to the unstimulated breaths of the same patient and theprevious stimulated breaths of the same patient that are stored in thedevice memory.

The general purpose of the feedback control is to achieve the desiredextension of the breath at the minimum expanding of stimulation energyand with a minimum additional inspired tidal volume that can result fromstimulation and additional diaphragmic contraction. Closed loop controlalgorithms such as PID controllers can be used to meter the adjustmentsbased on the real time information and the process history.

FIG. 3 is a stylized representation of tidal volume, airflow, and anillustrative stimulation therapy in accordance with embodiments of theinvention. Tidal volume waveform 301 and airflow waveform 320 are shownduring hyperpnea. Breaths 303, 304 and 305 sequentially increase inamplitude by increments of tidal volume that exceed 20% of the precedingbreath. They therefore meet the criteria for stimulation set by anillustrative software algorithm for the detection of hyperpnea. Inaddition a tidal volume threshold criterion may set as illustrated bythe by the line 308. In some embodiments, the stimulation pulse train310 is activated only if the breath tidal volume 309 exceeds thethreshold 308.

In this embodiment, stimulation is applied at the peak inspiration timepoint 311 when the breath phases change from inspiration to expiration.In this example three stimulation pulse trains 310, 312 and 313 areapplied to three sequential breaths. In similar embodiments, stimulationmay be applied at any point during inspiration. In those embodimentswhere the stimulation is applied at different points of inspiration, itmay be helpful to fashion the stimulation pulse train so that thestimulation is applied somewhat gradually to move the diaphragm to acontracted position more gently to avoid arousing a sleeping patient.

In some embodiments, an additional stimulation criterion may be set by ablanking period 315. Blanking period can be set, for example, equal tothe duration of time that is between 25% and 90% of the duration of anaverage spontaneous (unstimulated) breath for the treated patient or tosome fixed value such as, for example, one second. The blanking periodis applied to avoid double triggering. During the blanking period 315,stimulation is not allowed even if all other criteria are met. Theblanking period can be implemented as a software time counter thatstarts counting after a stimulation pulse train is applied. Inembodiments where the stimulation is not coordinated with the peak ofinspiration, the blanking period may be shorter, particularly if thestimulation is configured to hold the lung “still” for a relatively longtime.

FIG. 4 is a stylized representation of a stimulation protocol inaccordance with embodiments of the invention. In this embodiment, anadjustment is made based on the results of the stimulation of theprevious breath, but it is understood that such an adjustment can beperformed based on the acquired respiratory data collected over severalstimulated breaths or within the same breath.

FIG. 4 shows a representation of a respiratory waveform during ahyperpnea cycle. Breath 402 is not stimulated. Breath 403 is the firststimulated breath of the cycle. Stimulation pulse train 404 is appliedshortly after the natural inspiration phase 405 of the breath 403 hasreached the natural peak inspiration point 408. In this case thestimulation energy of the pulse train 404 may be excessive. Naturalinspiration 405 is followed by the additional inspiration 407 caused bythe stimulation and that results in the added tidal volume 409.Simultaneously with the stimulated lung inspiring the additional volume409, the contralateral unstimulated lung starts expiring air 410. Thisis the first of two expirations that have been seen during theunilateral (single lung) stimulation performed according to embodimentsof the invention. In this example, first lung expiration 410 stops whenapproximately 50% of air inhaled by the patient during the inspirationphase 405 is exhaled and the patient's lungs enter into a plateau orstill period 411. This still period 411 can be shortened or prolonged bydecreasing or increasing the duration of the stimulation pulse train404. When stimulation 404 stops, the second (stimulated) lung enters thesecond expiration phase of the stimulated breath cycle 412 that ends atthe point when both lungs are substantially deflated 413. It is believedthat the stimulated lung's stretch receptor feedback inhibits the nextbreath, which can be started by the autonomic control system afterexpiration is completed.

Breath 401 is stimulated by the pulse train 405. The stimulation energyof the pulse train 405 is reduced compared to the pulse train 404 basedon the analysis of the breath 403. Reduction can be achieved by reducingthe electric current of pulse train, the duration of pulse train or thefrequency of stimulation. The reduction of energy has the effect on theshape of the breath 401 compared to the breath 403. Stimulation 405starts at the peak of natural inspiration 414 and there is nosignificant additional inspiration or added tidal volume caused by thestimulation. Expiration of the unstimulated lung 415 is followed by aplateau 416 that is followed by the expiration of the stimulated lung417. It is understood that the optimization of the stimulation energycan be performed in small increments from one stimulated breath toanother and involve feedback mechanisms such as a digital PI or PIDregulators and other tools commonly used by engineers to design feedbackloops and controls.

In some embodiments, the stimulation energy is allowed or designed toadd tidal volume to an intrinsic breath. This is of course true wherethe breath is a diminished or apnea-hypopnea breath, but it also may bethe case that some therapies are designed or allowed to add tidal volumeto intrinsic breaths during normal respiration or hyperpnea(particularly near the start or end of the hyperpnea phase). In thesecases calibration of the stimulation signal may be based on factorsother than a desire to minimize additional inspiration caused bystimulation.

FIG. 5 is a stylized representation of tidal volume during a CSR cyclewith mixed apnea and several treatment protocols in accordance withembodiments of the invention. The CSR cycle is the same as is shown anddescribed with respect to FIG. 1. The various treatment protocols, ormodes, are shown in a simplified fashion below the representation of theCSR cycle. The effects of the stimulation profile on the tidal volumeare not shown in this Figure, but will be discussed here and elsewhere.Mode 1 is a stimulation that begins 500 upon the detection of hyperpneaand continues through the majority of the hyperpnea cycle. It isbelieved that holding at least one lung still during the hyperpnea cyclereduces respiration during that cycle and thus reduces the likelihood ofventilatory overshoot and a subsequent reduced breathing period thatcould result from such an overshoot.

Mode 2 is a stimulate and hold mode similar to mode 1. In mode 2,apnea-hypopnea is detected at 502. After a delay of an adjustable setamount 504, a stimulation pulse train is initiated 506 and held throughthe majority of the hyperpnea cycle. As with any of the modes, thestimulation may be shaped to gradually capture and contract thediaphragm so as to be less likely to arouse the patient or causediscomfort.

Mode 3 stimulates and holds at least one hemidiaphragm based on ahistorical average duration of hyperpnea and apnea-hypopnea cycles. If apatient has not immediately responded to therapy, mode 3 would stimulateand hold based on historical durations of apnea-hypopnea 510 andhyperpnea 512. The stimulation 512 and blanking period 510 would bebased on these average durations and not on any real-time detection ofbreathing parameters. This mode might be useful if a patient's movementduring sleep makes it difficult to measure respiration parametersaccurately, for example.

Mode 4 stimulates and holds at least one hemidiaphragm for randomperiods 514 at random intervals 516. This mode may be effective becauseholding at least one lung still during apnea-hypopnea has little effect,while desirable effects flow from holding one lung still during periodsof hypopnea. This mode may be effective for some patients and is verysimple to implement and manage. This mode may be automatically triggeredupon detection of sleep by the use of an accelerometer and/or positionsensor or any other means known in the art. Sleep detection may be usedto trigger or terminate or otherwise manage any of these modes.

FIG. 6 is a stylized representation of tidal volume during a CSR cyclewith mixed apnea and several treatment protocols in accordance withembodiments of the invention. The CSR cycle is the same as is shown anddescribed with respect to FIG. 1. The various treatment protocols, ormodes, are shown in a simplified fashion below the representation of theCSR cycle. The effects of the stimulation profile on the tidal volumeare not shown in this Figure, but will be discussed here and elsewhere.Mode 5 comprises a series of short stimulation signals 602 duringapnea-hypopnea. This mode could be employed by detecting actualapnea-hypopnea episodes and stimulating for the majority of the durationof the reduced autonomic breathing. The short pulses of mode 5 aredesigned to stimulate respiration during the apnea-hypopnea phase whereless than normal respiratory drive is present. Each signal is intendedto create or augment a breath.

When employing mode 5, it may be important not to contribute to thehyperventilation or excessive ventilation. Mode 5 will therefore oftenbe configured to stimulate breathing at below mean ventilation levels.One possible way of accomplishing this would be to stimulate one lung ata time. The stimulation could also be set to send the stimulationsignals at 50% of normal breathing rate, 50% of the apnea hyperpneaperiodic breathing cycle, or some arbitrary low number such as 6-10breaths per minute or it could be set to stimulate for 50% of theapnea-hypopnea duration, for example. The stimulation of mode 5 duringapnea-hypopnea may reduce oxygen desaturation which may reducerespiratory overshoot by keeping the blood gases at a more consistentlevel.

Patients with mixed apnea may also differ in the degree of airwayobstruction (obstructive component of apnea). In general, the airwaydiameter may fluctuate with the CSR cycle. The airway may be more openduring hyperpnea and gradually more closed during a decrescendo ofhyperpnea and apnea-hypopnea. In many cases, significant airway closureis observed towards the end of apnea-hypopnea. This can contribute toarousals at the beginning of hyperpnea, when the patient startsbreathing against the closed or significantly obstructed airway. In thisregard it may be advisable in some cases to engage the stimulation ofmode 5 in the early stages of apnea-hypopnea when airway closure may beless likely.

Mode 6 comprises a series of short stimulation bursts 604 throughout theCSR cycle. It has been observed that in some patients stimulatingthroughout CSR without regard to synchronizing the stimulations tobreathing or any phase of breathing may “train” the poorly functioningautonomic control to engage in more regular control of breathing. Thestimulation signal in mode 6 may be on the order of one to two seconds.

It has been observed that the crescendo-decrescendo pattern of a typicalhyperpnea cycle may represent a relatively strong respiratory driveearly in the hyperpnea cycle that gradually decreases during thedecrescendo phase of the hyperpnea. It is believed that initiating amode 6 stimulation pattern after the midpoint of the hyperpnea cycle maybe effective in maintaining a regular breathing pattern for the durationof the stimulation and may actually result in regular autonomicbreathing once the stimulation is terminated.

Mode 7 comprises a series of short stimulation bursts 602 duringapnea-hypopnea with an extended stimulation and hold during hyperpnea606. It has been observed that the drive to hyperventilate in CSRpatients may vary throughout the night. For example, it may be mostsevere early in the sleep cycle and may wane some as the patient fallsmore deeply into sleep or as therapies mitigate the drive. It may beadvisable in some cases to implement mode 7 early in a sleep period andthem move to mode 1 or another mode as the therapy mitigates thedisordered breathing.

The reverse may also be true, as the ultimate goal is to stabilizebreathing. A patient therapy may be started on mode 1 with the hope thatattenuating respiration during hyperpnea will reduce respiratoryovershoot and result in autonomic breathing replacing apnea-hypopnea. Ifmode 1 is not effective in breaking the CSR cycle after some time, thedevice could switch to mode 7 or some other mode to provide someventilation during apnea-hypopnea cycles and reduce blood oxygendesaturation incidents.

Mode 8 comprises a number of longer segmented signals 608 duringhyperpnea. The signals are separated by intervals 610 so that thesignals hold at least one hemidiaphragm still during hyperpnea forseveral discontinuous periods.

All of the modes just described, and others that will occur to those ofskill in the art upon reading this disclosure, may be combined into asingle therapy delivery device. These modes may be selected based on apatient's response to therapy and other factors considered bypractitioners that treat disordered breathing.

FIG. 7 is a flowchart of a detection and treatment protocol inaccordance with embodiments of the invention. Respiratory data of apatient is gathered 700 from sensors capable of detecting signalsrepresentative of respiration frequency and amplitude. The data is thenanalyzed 701 to determine if the patient is experiencing an episode thatcan be characterized as apnea-hypopnea. Clinically, apnea is defined as10 seconds or more of very little (less than 10% of normal for thepatient) breathing or no breathing at all. For practical purposesapnea-hypopnea can be detected as 4-9 seconds without breathing or withvery shallow breathing. Very shallow breathing can be defined as, forexample, less than 5-20% of highest tidal volume previously detectedduring the previous CSR cycle or over selected several minutes ofspontaneous ventilation or as less than 10% of patient's normal,non-periodic breathing. The thresholds for apnea-hypopnea detection canbe automatically periodically adjusted based on the respiratoryinformation stored in the device memory or adjusted by a practitionerbased on characteristics of the individual patient.

If apnea-hypopnea is detected, it can be used to enable therapy during afollowing hyperpnea cycle. The stimulation device may be “armed” 702upon detection of apnea-hypopnea and would be set to intervene andmoderate respiratory overshoot upon the onset of hyperpnea. Interventioncan occur within the same CSR cycle or during one of the followingcycles.

In one embodiment the protocol will detect apnea-hypopnea, wait for thefirst breath that meets the hyperpnea criteria 703, and startstimulation as soon as the first breath occurs following apnea-hypopnea.In this embodiment, the hyperpnea criteria may be a simple amplitudethreshold that is normally crossed as the patient moves fromapnea-hypopnea to hyperpnea.

Another embodiment assumes a relatively long stimulation duration of30-60 seconds. In this embodiment hyperpnea is suppressed, as in others,and stimulation may or may not be synchronized toinspiration-expiration.

In another embodiment, the device detects hyperpnea 703 by analyzing therespiratory waveform over several breaths. Hyperpnea can be detected703, for example, by three sequential breaths where the tidal volume ofthe next breath exceeds the tidal volume of the previous breath by 20%or more. If such sequentially escalating breaths are detected, a devicemay apply stimulation to the following breath or several breaths 704 ifarmed 705. It can be expected that the device will intervene and extendat least one breath after, for example, the first 4-10 breathes ofhyperpnea are detected and analyzed. Other methods of detecting ordeclaring hyperpnea may be used without departing from the spirit ofthis disclosure. Some patients may have hyperpneas that do not followthe crescendo-decrescendo pattern that is frequently found in CSR, andhyperpnea detection criteria can be set on a case-by-case basis.

The protocol may decide 707 to adjust the parameters of stimulation 706based on the data collected 700 from the intervention (the physiologicresponse to stimulation) during one or more previous CSR cycles. Theseparameters can include: stimulation duration, stimulation energy and thenumber of extended breaths.

FIG. 8 is a flowchart of a detection and treatment protocol inaccordance with embodiments of the invention. This protocol can beexecuted alone or in combination with other protocols. For example, thisprotocol could be executed within the block 704 in FIG. 7. It couldrepresent the decisions made within one breath after the hyperpnea isidentified in block 703 of FIG. 7. In the event that this protocol isnested within the protocol of FIG. 7, the redundant steps (i.e.,hyperpnea detection) would not be performed.

In the embodiment of FIG. 8 as a stand-alone protocol, respiratorywaveform data is acquired 801 from a respiration sensor in real time,for example every 10 milliseconds. The detected beginning of theinspiration phase of the breath starts the breath analysis 802. As thedata points are acquired, a value representative of inspired tidalvolume gradually increases. If hyperpnea is not detected 803, furtherrespiratory waveform data is gathered 801. If hyperpnea is detected,parameters such as tidal volume at the end of inspiration, inspirationduration and the rate of inspiration (volume divided by time) arecalculated and analyzed 804.

The protocol may decide 805 to trigger or not trigger the application ofa stimulation pulse train or even to abort the pulse train before thenormal duration time based on this constantly updated data stream andanalysis. The breath analysis 804 may include, without limitations, thefollowing tests:

If the inspiration duration is less than a preset time of, for example,0.5 sec. or is less than 75% of the inspiration time of an averagebreath for this patient, or some predetermined fraction of theinspiration time of the previous breath, stimulation may not betriggered. Conversely if the inspiration duration is significantlylonger than expected, stimulation also may not be triggered.

FIG. 9 is a flowchart of a stimulation adjustment protocol in accordancewith embodiments of the invention. The protocol of FIG. 9 may be used toaccomplish the signal adjustment described in relation to FIG. 4. Afterthe stimulated breath 901 is substantially completed, the additionaltidal volume as compared to an unstimulated breath is calculated 902. Ifan overstimulation is detected 903, such as for example an additional10% of tidal volume is inhaled by the patient after the natural peak ofinspiration is reached, the energy of stimulation is adjusted 904 beforethe stimulation of the next stimulated breath 905. The adjustment mayconstitute a 10% reduction of the stimulation current or signalduration.

FIG. 10 is a flowchart of a stimulation adjustment protocol inaccordance with embodiments of the invention. It is possible that, theadjustment of energy illustrated by FIG. 9 can result in the loss ofrespiratory inhibition or, in the case of nerve stimulation, the loss ofnerve capture. This loss of inhibition can be detected by the absence ofthe stimulated breath plateau (See FIG. 4 and related discussion) inresponse to the application of stimulation 1001 or by the increase ofrespiratory rate indicated by the absence of the expected delay 1002before the next breath 1003. If the breath is not delayed or the plateauis not detected, the stimulation energy can be increased 1004 to beapplied to the next stimulated breath 1005.

The general purpose of the feedback control is to achieve the desiredcontraction of the diaphragm with the minimum expanding of stimulationenergy and with a minimum additional inspired tidal volume that canresult from stimulation and additional diaphragmic contraction. Closedloop control systems such as PID controllers can be used to meter theadjustments based on the real time information and the process history.

An alternative method of determining if stimulation capturing thediaphragm is to apply a short stimulation signal during apnea-hypopnea.A short stimulation envelope, for example 2 seconds long, can be appliedwhen no significant natural breathing occurs. The response to thisstimulation can be measured as tidal volume or lung volume change. Sucha capture test could be performed periodically and the energy ofstimulation can be adjusted if indicated. Such test signals duringapnea-hypopnea allow detection of stimulation capture with lessinterference from natural breathing.

FIG. 11 is a flowchart of a breath detection protocol in accordance withembodiments of the invention. A signal (N) is captured 1100 from arespiration sensor configured to sense respiratory effort of a patient.The sensor could be an impedance sensor, an accelerometer, an externalrespiration belt, or any other sensor known in the art. When theprotocol is in the inspiration mode 1102, it counts the signal based ona sample frequency 1104. The protocol begins with a “MAX” value set atthe system minimum and a “MIN” value set to the system maximum. Theprotocol originally assumes the patient is in inspiration and comparesthe measured signal to the recorded MAX. If the signal is greater thanMAX 1106, MAX is reset to the signal value 1108. This continues untilthe signal is less than MAX, at which time a noise detection protocol1110 checks that the signal has not dropped an unreasonable amount,which might indicate a signal interruption or noise, and that the countsince the beginning of inspiration is greater than a preset orcalculated minimum breath duration. If the detected peak of inspirationindicated by the decreasing signal is determined to be real, anamplitude representative of tidal volume is calculated 1112 bysubtracting the new MAX from the most recently determined VALLEY(discussed below). If this amplitude passes a noise threshold 1114 theexpiration loop is initiated 1116 and a PEAK value is assigned the valueof MAX, or the most recent signal.

The expiration loop 1118 begins with a counter 1120 that accumulatessignal data during the expiration cycle. If the signal is less than MIN1126, MIN is reset to the signal value 1124. This continues until thesignal is greater than MIN, at which time a noise detection protocol1128 checks that the signal is not unreasonably greater than MIN andthat the count since the beginning of expiration is greater than apreset or calculated minimum breath duration. If the detected valley ofexpiration indicated by the now-increasing signal is determined to bereal, an amplitude representative of tidal volume is calculated 1130 bysubtracting the new MIN from the most recently determined PEAK. If thisamplitude passes a noise threshold 1132, the inspiration loop isinitiated 1134 and a VALLEY value is assigned to the value of MIN, orthe most recent signal.

From this protocol, or others using the same basic framework or thatwill occur to those of skill in the art upon reading this disclosure,values for breath frequency or periodicity, amplitude or tidal volume,inspiration duration, expiration duration, cyclic changes of tidalvolume, onset an peak of inspiration, onset and peak of expiration andothers may be determined. Averages over time or over relevant periods oftime may also be calculated. For example, a baseline breath duration maybe calculated by measuring breath periodicity over a period of time andcalculating an average value. Such baseline development may happen whilea patient is awake or at other times when disordered breathing is lesslikely. Even during periods of CSR, average breath duration can be takenover several cycles of breathing and should remain reasonably constantand provide a good baseline.

FIG. 12 is a flowchart of a breath detection protocol in accordance withembodiments of the invention. This protocol is another alternativemethod of determining cycles of inspiration and expiration andassociated breathing data. A signal (N) is captured 1200 from arespiration sensor configured to sense respiratory effort of a patient.If the signal is processed through the inspiration loop 1202, the slopeof the signal and the previous signal is determined and compared to zero1204 to look for an inflection point. If the slope of the signals waspositive and is now negative, and a noise threshold test is passed, itcan be determined that a peak of inspiration has occurred. The peakvalue is recorded 1206 and the expiration module 1208 commences. Theexpiration module 1210 compares the slope of the data points, generallynegative throughout expiration depending on the respiration sensor used,until the slope becomes positive. Once the slope of the signals changesfrom negative to positive, and a noise threshold test is passed, it canbe determined that a valley of expiration has occurred and the valleycan be recorded 1212 and the inspiration module can begin. This protocolcan determine respiration qualities such as breath frequency orperiodicity, amplitude or tidal volume, inspiration duration, expirationduration, cyclic changes of tidal volume, onset an peak of inspiration,onset and peak of expiration, for example.

FIG. 13 is a flowchart of an apnea-hypopnea detection protocol inaccordance with embodiments of the invention. The protocol begins when arespiration peak is detected 1300 in accordance with a protocol such asthose shown in FIGS. 11 and 12, or others. The respiration rate is thencalculated 1302 based on accumulated data either in the peak detectionmodule or this module. A baseline breath amplitude is determined 1306for the patient. Such a baseline may be set based on breathing datacollected during the day, in the case of a sleep apnea patient, or atany other time that regular breathing may be tracked. Alternatively, abaseline breath amplitude may be determined by a practitioner and presetinto the protocol. However determined, the protocol checks to seewhether all breaths in the last ten seconds lower than 30% of thebaseline 1306. If so, apnea-hypopnea is detected. Other criteria couldbe used to detect and declare and episode of apnea-hypopnea, and all arecontemplated within the scope of this disclosure.

FIG. 14 is a flowchart of a hyperpnea detection protocol in accordancewith embodiments of the invention. The protocol begins when arespiration peak is detected 1400 in accordance with a protocol such asthose shown in FIGS. 11 and 12 or others. The protocol of FIG. 14determines if the peak is higher than 30% of a baseline breath amplitude1402 determined as described with respect to FIG. 13. If there is nosuch peak, the module waits for the next peak from the peak detectionmodule 1400. Once the module detects a breath peak higher than 30% ofthe baseline 1402 it checks for a preceding apnea by determining if allpeaks during the last 10 seconds were lower than 30% of baseline 1404.If both conditions 1402 and 1404 are met, the start of a hyperpnea cycleis detected 1408. The criteria for steps 1402 and 1404 may be modifiedas desired without departing from the spirit of this disclosure.

FIG. 15 is a flowchart of a hyperpnea detection protocol in accordancewith embodiments of the invention. The protocol begins when arespiration peak is detected 1500 in accordance with a protocol such asthose shown in FIGS. 11 and 12 or others. The protocol of FIG. 15determines the slope of the last three detected peaks and compares theslope to a predetermined or historically determined threshold 1502. Ifthe slope of the three peaks exceeds the threshold, the protocoldetermines whether all peaks recorded during the ten seconds prior tothese three peaks had an amplitude lower than 30% of a baseline breathamplitude 1504. If both conditions 1502 and 1504 are met, the start of ahyperpnea cycle 1508 is detected. The criteria for steps 1402 and 1404may be modified as desired without departing from the spirit of thisdisclosure.

FIG. 16 is a representation of a stimulation signal in accordance withembodiments of the invention. The stimulation signal lasts a stimulationduration or signal duration 1602. The stimulation signal is made up of aseries of pulses 1604 represented by vertical lines in FIG. 16. In thisexample, when the stimulation is initiated, the current begins at a baseor first level 1606. In some embodiments, the base current level 1606 is1-2 milliamps (mA). The stimulation current amplitude then transitions1610 over a percentage of the total duration to a plateau or secondlevel 1608. In some embodiments, the plateau current level 1608 may bebetween 2-4 mA and the time to go from the base current level 1606 tothe plateau is about 30% 1610 of the total signal duration 1602. Thecurrent amplitude may transition 1610 from the base current level to theplateau current level in a linear, exponential, or elliptical fashion orany other transition shape that may be useful. The gradual nature ofthis transition 1610 may help reduce patient discomfort and reduce oreliminate arousals during sleep. The current amplitude may alsotransition downward 1612 near the end of the stimulation signal in asimilar fashion as the initial transition 1610. This may release thestimulation more gradually and may provide similar benefits for apatient.

The stimulation pulses 1604 in this example may be delivered at afrequency of 20 Hz and last for a period of 150 μsec. The stimulationduration or signal duration 1602 includes the entire time from thatpulses are delivered including transition pulses 1610, 1612.

FIG. 17 shows experimental results of treatment of disordered breathingcarried out in accordance with embodiments of the invention. The patientis experiencing CSR as shown by periods of hyperpnea 1702 andapnea-hypopnea 1708. The hyperpnea exhibits what is commonly referred toas a crescendo 1704-decrescendo 1706 pattern. The patient's breathingrate during the disordered breathing episodes is approximately 18breaths per minute. Stimulation signals 1712 are initiated duringhyperpnea after the midpoint 1710 of the hyperpnea cycle. Thestimulation signals extend the breath duration and slow the breathingrate from 18 breaths per minute to 11 breaths per minute. Thestimulation signals are applied to additional future breaths 1714occurring after the normal duration of the hyperpnea cycle. As can beobserved, the CSR cycle is broken and the deleterious effects of CSRincluding, but not limited to, pulse rate variations, blood gasvariations, oxygen desaturation are reduced or eliminated. It isbelieved that long term health benefits will also accrue, particularlyfor heart failure patients.

The extension of breath duration may not result in a lowered breathingrate as measured by breaths per minute. In cases where, for example, apatient is in hyperpnea for 40 seconds and apnea-hypopnea for 20seconds, a measured breathing rate of 20 breaths per minute might resultfrom a rate of one breath per two seconds (two-second breaths) duringthe 40-second hyperpnea with little or no breathing activity during theapnea-hypopnea. Extending the breath duration and eliminating orreducing the apnea-hypopnea may, for example, result in a breathing rateof one breath per three seconds (three-second breaths) over an entireminute, which would still result in a measured breathing rate of 20breaths per minute.

FIG. 18 shows experimental results of treatment of disordered breathingcarried out in accordance with embodiments of the invention. The patientis experiencing CSR as shown by periods of hyperpnea 1802 andapnea-hypopnea 1808. A stimulation signal 1812 is delivered to onehemidiaphragm at the start of a hyperpnea cycle and the stimulated lungis held open starting at time 1804. The stimulation signal duration isgreater than 50% of a normal hyperpnea duration and the stimulated lungis stilled for that entire time. Muted respiration signals 1806 can beseen throughout the stimulation, likely from the contralateral lungstill responding to autonomic signals. The stimulation is repeated 1812at the start of the next hyperpnea until the CSR cycle is broken.

While exemplary embodiments of this invention have been illustrated anddescribed, it should be understood that various changes, adaptations,and modifications may be made therein without departing from the spiritof the invention and the scope of the appended claims.

What is claimed is:
 1. A system for treating disordered breathing of ahuman being comprising: a stimulation lead having at least onestimulation electrode, wherein the stimulation lead is configured to beimplanted into a blood vessel proximate a phrenic nerve, wherein the atleast one stimulation electrode is configured to electrically stimulatethe phrenic nerve; a sensor configured to detect activity level of thehuman being; and an energy source, a pulse generator and circuitry, thecircuitry operative to receive a signal indicative of the activity levelof the human being from the sensor, wherein the circuitry is configuredto: cause detection of a hyperpnea episode based on a respirationsignal; cause the energy source and the pulse generator to triggerand/or terminate a train of stimulation pulses to the at least onestimulation electrode based on the activity level of the human beingindicative of sleep, wherein the train of stimulation pulses isinitiated during the detected hyperpnea episode, wherein stimulationpulses in the train of stimulation pulses are substantially uniformlyspaced in time, and wherein the energy source and the at least onestimulation electrode are configured to deliver the train of stimulationpulses, the train of stimulation pulses configured to extend a durationof time of at least one breath, the at least one breath being defined asa time from an onset of inhalation to the onset of inhalation of asuccessive breath.
 2. The system of claim 1, wherein the sensorconfigured to detect activity level comprises an accelerometerconfigured to detect the activity level of the human being.
 3. Thesystem of claim 1, wherein the sensor configured to detect activitylevel comprises an accelerometer configured to detect the activity levelof the human being, and the accelerometer also is configured to senserespiration of the human being and provide the respiration signal. 4.The system of claim 1 and further comprising a respiration sensorwherein the circuitry is configured to determine a duration of aCheyne-Stokes Respiration (CSR) episode based on the respiration signalfrom the respiration sensor, wherein the circuitry is configured todeliver a stimulation signal to the stimulation electrode during theCheyne-Stokes Respiration (CSR) episode while the sensor configured todetect activity level of the human being is sending a signal to thecircuitry indicative of the activity level of the human being at a levelindicative of sleep.
 5. The system of claim 4, wherein the train ofstimulation pulses are substantially uniformly spaced in time and aredelivered throughout the duration of the Cheyne-Stokes Respiration (CSR)episode.
 6. The system of claim 4 wherein each simulation pulse in thetrain of stimulation pulses is in a range of one to two seconds.
 7. Thesystem of claim 4, wherein the respiration sensor senses transthoracicimpedance.
 8. A system for treating disordered breathing of a humanbeing comprising: a stimulation lead having at least one stimulationelectrode wherein the lead is configured to be located in a veinproximate a phrenic nerve, such that the at least one stimulationelectrode is configured to transvenously capture the phrenic nerve; arespiration sensor; a sensor configured to detect sleep by the humanbeing; and an energy source, a pulse generator and circuitry, thecircuitry operative to receive a signal indicative of a position oractivity level of the human being from the sensor configured to detectsleep, and wherein the circuitry is configured to: cause detection of ahyperpnea episode based on a signal from the respiration sensor; causethe energy source and the pulse generator to trigger and/or terminate atrain of stimulation pulses to the at least one stimulation electrodebased on the detected sleep; wherein the train of stimulation pulses isinitiated during the detected hyperpnea episode; wherein stimulationpulses in the train of stimulation pulses are substantially uniformlyspaced in time and delivered by the at least one stimulation electrodeduring the detected hyperpnea episode to extend a duration of time of atleast one breath, the at least one breath being defined as a time froman onset of inhalation to the onset of inhalation of a successivebreath.
 9. The system of claim 8, wherein the sensor configured todetect sleep comprises an accelerometer configured to detect movement ofthe human being.
 10. The system of claim 8, wherein the train ofstimulation pulses is delivered throughout a duration of the detectedhyperpnea episode.
 11. The system of claim 10, wherein each stimulationpulse in the train of stimulation pulses is in the range of one to twoseconds.
 12. The system of claim 8, wherein the respiration sensorsenses transthoracic impedance.